SummaryBrain-inspired (neuromorphic) computing has recently demonstrated advancements in pattern and image recognition as well as classification of unstructured (big) data. However, the volatility and energy required for neuromorphic devices presented to date significantly complicate the path to achieve the interconnectivity and efficiency of the brain. In previous work, recently published in Nature Materials, the PI has demonstrated a low-cost solution to these drawbacks: an organic artificial synapse as a building-block for organic neuromorphics. The conductance of this single synapse can be accurately tuned by controlled ion injection in the conductive polymer, which could trigger unprecedented low-energy analogue computing.
Hence, the major challenge in the largely unexplored field of organic neuromorphics, is to create an interconnected network of these synapses to obtain a true neuromorphic array which will not only be exceptionally pioneering in materials research for neuromorphics and machine-learning, but can also be adopted in a multitude of vital medical research devices. BIOMORPHIC will develop a unique brain-inspired organic lab-on-a-chip in which microfluidics integrated with sensors, collecting characteristics of biological cells, will serve as input to the neuromorphic array. BIOMORPHIC will combine modular microfluidics and machine-learning to develop a novel platform for low-cost lab-on-a-chip devices capable of on-chip cell classification.
In particular, BIOMORPHIC will focus on the detection of circulating tumour cells (CTC). Current methods for the detection of cancer are generally invasive, whereas analysing CTCs in blood offers a highly desired alternative. However, accurately detecting and isolating these cells remains a challenge due to their low prevalence and large variability. The strength of neuromorphics precisely lies in finding patterns in such variable data, which will result in a ground-breaking CTC classification lab-on-a-chip.

Brain-inspired (neuromorphic) computing has recently demonstrated advancements in pattern and image recognition as well as classification of unstructured (big) data. However, the volatility and energy required for neuromorphic devices presented to date significantly complicate the path to achieve the interconnectivity and efficiency of the brain. In previous work, recently published in Nature Materials, the PI has demonstrated a low-cost solution to these drawbacks: an organic artificial synapse as a building-block for organic neuromorphics. The conductance of this single synapse can be accurately tuned by controlled ion injection in the conductive polymer, which could trigger unprecedented low-energy analogue computing.
Hence, the major challenge in the largely unexplored field of organic neuromorphics, is to create an interconnected network of these synapses to obtain a true neuromorphic array which will not only be exceptionally pioneering in materials research for neuromorphics and machine-learning, but can also be adopted in a multitude of vital medical research devices. BIOMORPHIC will develop a unique brain-inspired organic lab-on-a-chip in which microfluidics integrated with sensors, collecting characteristics of biological cells, will serve as input to the neuromorphic array. BIOMORPHIC will combine modular microfluidics and machine-learning to develop a novel platform for low-cost lab-on-a-chip devices capable of on-chip cell classification.
In particular, BIOMORPHIC will focus on the detection of circulating tumour cells (CTC). Current methods for the detection of cancer are generally invasive, whereas analysing CTCs in blood offers a highly desired alternative. However, accurately detecting and isolating these cells remains a challenge due to their low prevalence and large variability. The strength of neuromorphics precisely lies in finding patterns in such variable data, which will result in a ground-breaking CTC classification lab-on-a-chip.

Max ERC Funding

1 498 726 €

Duration

Start date: 2019-01-01, End date: 2023-12-31

Project acronymBioNanoPattern

ProjectProtein nano-patterning using DNA nanotechnology; control of surface-based immune system activation

Researcher (PI)Thomas Harry SHARP

Host Institution (HI)ACADEMISCH ZIEKENHUIS LEIDEN

Call DetailsStarting Grant (StG), LS9, ERC-2017-STG

SummaryProtein nanopatterning concerns the geometric arrangement of individual proteins with nanometre accuracy. It is becoming apparent that protein nanopatterns are essential for cellular function, and have roles in cell signalling and protection, phagocytosis and stem cell differentiation. Recent research indicates that our immune system is activated by nanopatterned antibody platforms, which initiate the classical Complement pathway by binding to the first component of Complement, the C1 complex. DNA nanotechnology can be used to form self-assembled nanoscale structures, which are ideal for use as templates to pattern proteins with specific geometries and nanometre accuracy. I propose to use DNA to nanopattern antigens and agonistic aptamers with defined geometry to study and control Complement pathway activation by the C1 complex.
To develop and demonstrate the potential use of DNA to nanopattern proteins, the first aim of this proposal is to design DNA nanotemplates suitable for patterning antibody-binding sites. Antibodies and C1 will bind with specific geometry, and the relationship between antibody geometry and Complement activation will be assessed using novel liposome assays. Using DNA to mimic antigenic surfaces will enable high-resolution structure determination of DNA-antibody-C1 complexes, both in solution and on lipid bilayer surfaces, using phase plate cryo-electron microscopy to elucidate the structure-activation relationship of C1.
The second aim of this proposal is to evolve agonistic aptamers that directly bind to and activate C1, and incorporate these into DNA nanotemplates. These nanopatterned aptamers will enable further study of C1 activation, and allow direct targeting of Complement activation to specific cells within a population of cell types to demonstrate targeted cell killing. This may open up new and highly efficient ways to activate our immune system in vivo, with potential for targeted anti-tumour immunotherapies.

Protein nanopatterning concerns the geometric arrangement of individual proteins with nanometre accuracy. It is becoming apparent that protein nanopatterns are essential for cellular function, and have roles in cell signalling and protection, phagocytosis and stem cell differentiation. Recent research indicates that our immune system is activated by nanopatterned antibody platforms, which initiate the classical Complement pathway by binding to the first component of Complement, the C1 complex. DNA nanotechnology can be used to form self-assembled nanoscale structures, which are ideal for use as templates to pattern proteins with specific geometries and nanometre accuracy. I propose to use DNA to nanopattern antigens and agonistic aptamers with defined geometry to study and control Complement pathway activation by the C1 complex.
To develop and demonstrate the potential use of DNA to nanopattern proteins, the first aim of this proposal is to design DNA nanotemplates suitable for patterning antibody-binding sites. Antibodies and C1 will bind with specific geometry, and the relationship between antibody geometry and Complement activation will be assessed using novel liposome assays. Using DNA to mimic antigenic surfaces will enable high-resolution structure determination of DNA-antibody-C1 complexes, both in solution and on lipid bilayer surfaces, using phase plate cryo-electron microscopy to elucidate the structure-activation relationship of C1.
The second aim of this proposal is to evolve agonistic aptamers that directly bind to and activate C1, and incorporate these into DNA nanotemplates. These nanopatterned aptamers will enable further study of C1 activation, and allow direct targeting of Complement activation to specific cells within a population of cell types to demonstrate targeted cell killing. This may open up new and highly efficient ways to activate our immune system in vivo, with potential for targeted anti-tumour immunotherapies.

Max ERC Funding

1 499 850 €

Duration

Start date: 2018-01-01, End date: 2022-12-31

Project acronymBIOSUSAMIN

ProjectThe design and development of efficient biocatalytic cascades and biosynthetic pathways for the sustainable production of amines

Researcher (PI)Francesco Mutti

Host Institution (HI)UNIVERSITEIT VAN AMSTERDAM

Call DetailsStarting Grant (StG), LS9, ERC-2014-STG

SummaryThe objective of this project is to design and develop biocatalytic cascades, using purified enzymes in vitro, as well as biosynthetic pathways in whole cell microbial organisms. These biocatalytic cascades and biosynthetic pathways will be developed for the synthesis of chiral and achiral amines that are of particular interest for the chemical industry. The amine functionality will be introduced using amine dehydrogenases (AmDHs) as biocatalysts in the pivotal core enzymatic step. AmDHs are a new class of enzymes that have recently been obtained by protein engineering of wild-type amino acid dehydrogenases. However, only two AmDHs have been generated so far and, moreover, they show a limited substrate scope. Therefore protein engineering will be undertaken in order to expand the substrate scope of the already existing AmDHs. In addition, novel AmDHs will be generated starting from different wild-type amino acid dehydrogenases as scaffolds, whose amino acid and DNA sequences are available in databases, literature, libraries, etc. In particular, protein engineering will be focused on the specific chemical targets that are the objectives of the designed biocatalytic cascades and in addition, screening for more diverse substrates will also be carried out. Finally, the AmDHs will be used in combination with other enzymes such as alcohol dehydrogenases, oxidases, alkane monooxygenases, etc., to deliver variously functionalised amines and derivatives as final products with elevated yields, perfect chemo- regio- and stereoselectivity, enhanced atom efficiency and minimum environmental impact. Such an approach will be realised through the design of new pathways that will convert inexpensive starting materials from renewable resources, encompassing the internal recycling of redox equivalents, the use of inorganic ammonia as nitrogen source and, if necessary, only molecular oxygen as the innocuous additional oxidant. Water will be the sole by-product.

The objective of this project is to design and develop biocatalytic cascades, using purified enzymes in vitro, as well as biosynthetic pathways in whole cell microbial organisms. These biocatalytic cascades and biosynthetic pathways will be developed for the synthesis of chiral and achiral amines that are of particular interest for the chemical industry. The amine functionality will be introduced using amine dehydrogenases (AmDHs) as biocatalysts in the pivotal core enzymatic step. AmDHs are a new class of enzymes that have recently been obtained by protein engineering of wild-type amino acid dehydrogenases. However, only two AmDHs have been generated so far and, moreover, they show a limited substrate scope. Therefore protein engineering will be undertaken in order to expand the substrate scope of the already existing AmDHs. In addition, novel AmDHs will be generated starting from different wild-type amino acid dehydrogenases as scaffolds, whose amino acid and DNA sequences are available in databases, literature, libraries, etc. In particular, protein engineering will be focused on the specific chemical targets that are the objectives of the designed biocatalytic cascades and in addition, screening for more diverse substrates will also be carried out. Finally, the AmDHs will be used in combination with other enzymes such as alcohol dehydrogenases, oxidases, alkane monooxygenases, etc., to deliver variously functionalised amines and derivatives as final products with elevated yields, perfect chemo- regio- and stereoselectivity, enhanced atom efficiency and minimum environmental impact. Such an approach will be realised through the design of new pathways that will convert inexpensive starting materials from renewable resources, encompassing the internal recycling of redox equivalents, the use of inorganic ammonia as nitrogen source and, if necessary, only molecular oxygen as the innocuous additional oxidant. Water will be the sole by-product.

SummaryA fundamental feature of language is that it allows us to reproduce what others have said. It is traditionally assumed that there
are two ways of doing this: direct discourse, where you preserve the original speech act verbatim, and indirect discourse,
where you paraphrase it in your own words. In accordance with this dichotomy, linguists have posited a number of universal
characteristics to distinguish the two modes. At the same time, we are seeing more and more examples that seem to fall
somewhere in between. I reject the direct indirect distinction and replace it with a new paradigm of blended discourse.
Combining insights from philosophy and linguistics, my framework has only one kind of speech reporting, in which a speaker
always attempts to convey the content of the reported words from her own perspective, but can quote certain parts verbatim,
thereby effectively switching to the reported perspective.
To explain why some languages are shiftier than others, I hypothesize that a greater distance from face-to-face
communication, with the possibility of extra- and paralinguistic perspective marking, necessitated the introduction of
an artificial direct indirect separation. I test this hypothesis by investigating languages that are closely tied to direct
communication: Dutch child language, as recent studies hint at a very late acquisition of the direct indirect distinction; Dutch
Sign Language, which has a special role shift marker that bears a striking resemblance to the quotational shift of blended
discourse; and Ancient Greek, where philologists have long been observing perspective shifts.
In sum, my research combines a new philosophical insight on the nature of reported speech with formal semantic rigor and
linguistic data from child language experiments, native signers, and Greek philology.

A fundamental feature of language is that it allows us to reproduce what others have said. It is traditionally assumed that there
are two ways of doing this: direct discourse, where you preserve the original speech act verbatim, and indirect discourse,
where you paraphrase it in your own words. In accordance with this dichotomy, linguists have posited a number of universal
characteristics to distinguish the two modes. At the same time, we are seeing more and more examples that seem to fall
somewhere in between. I reject the direct indirect distinction and replace it with a new paradigm of blended discourse.
Combining insights from philosophy and linguistics, my framework has only one kind of speech reporting, in which a speaker
always attempts to convey the content of the reported words from her own perspective, but can quote certain parts verbatim,
thereby effectively switching to the reported perspective.
To explain why some languages are shiftier than others, I hypothesize that a greater distance from face-to-face
communication, with the possibility of extra- and paralinguistic perspective marking, necessitated the introduction of
an artificial direct indirect separation. I test this hypothesis by investigating languages that are closely tied to direct
communication: Dutch child language, as recent studies hint at a very late acquisition of the direct indirect distinction; Dutch
Sign Language, which has a special role shift marker that bears a striking resemblance to the quotational shift of blended
discourse; and Ancient Greek, where philologists have long been observing perspective shifts.
In sum, my research combines a new philosophical insight on the nature of reported speech with formal semantic rigor and
linguistic data from child language experiments, native signers, and Greek philology.

SummaryRecent advances in cryptography yielded the blockchain technology, which enables a radically new and decentralized method to maintain authoritative records, without the need of trusted intermediaries. Bitcoin, a cryptocurrency blockchain application has already demonstrated that it is possible to operate a purely cryptography-based, global, distributed, decentralized, anonymous financial network, independent from central and commercial banks, regulators and the state.
The same technology is now being applied to other social domains (e.g. public registries of ownership and deeds, voting systems, the internet domain name registry). But research on the societal impact of blockchain innovation is scant, and we cannot properly assess its risks and promises. In addition, crucial knowledge is missing on how blockchain technologies can and should be regulated by law.
The BlockchainSociety project focuses on three research questions. (1) What internal factors contribute to the success of a blockchain application? (2) How does society adopt blockchain? (3) How to regulate blockchain? It breaks new ground as it (1) maps the most important blockchain projects, their governance, and assesses their disruptive potential; (2) documents and analyses the social diffusion of the technology, and builds scenarios about the potential impact of blockchain diffusion; and (3) it creates an inventory of emerging policy responses, compares and assesses policy tools in terms of efficiency and impact. The project will (1) build the conceptual and methodological bridges between information law, the study of the self-governance of technological systems via Science and Technology Studies, and the study of collective control efforts of complex socio-technological assemblages via Internet Governance studies; (2) address the most pressing blockchain-specific regulatory challenges via the analysis of emerging policies, and the development of new proposals.

Recent advances in cryptography yielded the blockchain technology, which enables a radically new and decentralized method to maintain authoritative records, without the need of trusted intermediaries. Bitcoin, a cryptocurrency blockchain application has already demonstrated that it is possible to operate a purely cryptography-based, global, distributed, decentralized, anonymous financial network, independent from central and commercial banks, regulators and the state.
The same technology is now being applied to other social domains (e.g. public registries of ownership and deeds, voting systems, the internet domain name registry). But research on the societal impact of blockchain innovation is scant, and we cannot properly assess its risks and promises. In addition, crucial knowledge is missing on how blockchain technologies can and should be regulated by law.
The BlockchainSociety project focuses on three research questions. (1) What internal factors contribute to the success of a blockchain application? (2) How does society adopt blockchain? (3) How to regulate blockchain? It breaks new ground as it (1) maps the most important blockchain projects, their governance, and assesses their disruptive potential; (2) documents and analyses the social diffusion of the technology, and builds scenarios about the potential impact of blockchain diffusion; and (3) it creates an inventory of emerging policy responses, compares and assesses policy tools in terms of efficiency and impact. The project will (1) build the conceptual and methodological bridges between information law, the study of the self-governance of technological systems via Science and Technology Studies, and the study of collective control efforts of complex socio-technological assemblages via Internet Governance studies; (2) address the most pressing blockchain-specific regulatory challenges via the analysis of emerging policies, and the development of new proposals.

Max ERC Funding

1 499 631 €

Duration

Start date: 2018-01-01, End date: 2022-12-31

Project acronymBOYS WILL BE BOYS?

ProjectBoys will be boys? Gender differences in the socialization of disruptive behaviour in early childhood

Researcher (PI)Judit Mesman

Host Institution (HI)UNIVERSITEIT LEIDEN

Call DetailsStarting Grant (StG), SH4, ERC-2009-StG

SummaryThe aim of the proposed project is to shed light on early childhood gender-differentiated socialization and gender-specific susceptibility to parenting within families in relation to disruptive behaviour in boys and girls in the first four years of life. The popular saying boys will be boys refers to the observation that boys show more disruptive behaviours (e.g., noncompliance or aggression) than girls, a pattern that has been confirmed frequently in scientific research. There is also evidence that parents treat boys differently from girls in ways that are likely to foster boys disruptive behaviour, and that boys are more susceptible to problematic family functioning than girls. The crucial question is whether gender differences in socialization, susceptibility to socialization, and children s behavioural outcomes are also salient when the same parents are doing the parenting of both a boy and a girl. Within-family comparisons are necessary to account for structural differences between families. To this end, families with two children born 22-26 months apart will be recruited from the general population. To account for birth order and gender-combination effects, the sample includes four groups of 150 families each, with the following sibling combinations: girl-boy, boy-girl, girl-girl, and boy-boy. The study has a four-wave longitudinal design, based on the youngest sibling with assessments at ages 12, 24, 36, and 48 months, because gender differences in disruptive behaviour develop during the toddler years. Each assessment consists of two home visits: one with mother and one with father, including observations of both children and of the children separately. Parenting behaviours will be studied in reaction to specific child behaviours, including aggression, noncompliance, and prosocial behaviours.

The aim of the proposed project is to shed light on early childhood gender-differentiated socialization and gender-specific susceptibility to parenting within families in relation to disruptive behaviour in boys and girls in the first four years of life. The popular saying boys will be boys refers to the observation that boys show more disruptive behaviours (e.g., noncompliance or aggression) than girls, a pattern that has been confirmed frequently in scientific research. There is also evidence that parents treat boys differently from girls in ways that are likely to foster boys disruptive behaviour, and that boys are more susceptible to problematic family functioning than girls. The crucial question is whether gender differences in socialization, susceptibility to socialization, and children s behavioural outcomes are also salient when the same parents are doing the parenting of both a boy and a girl. Within-family comparisons are necessary to account for structural differences between families. To this end, families with two children born 22-26 months apart will be recruited from the general population. To account for birth order and gender-combination effects, the sample includes four groups of 150 families each, with the following sibling combinations: girl-boy, boy-girl, girl-girl, and boy-boy. The study has a four-wave longitudinal design, based on the youngest sibling with assessments at ages 12, 24, 36, and 48 months, because gender differences in disruptive behaviour develop during the toddler years. Each assessment consists of two home visits: one with mother and one with father, including observations of both children and of the children separately. Parenting behaviours will be studied in reaction to specific child behaviours, including aggression, noncompliance, and prosocial behaviours.

Max ERC Funding

1 611 970 €

Duration

Start date: 2010-02-01, End date: 2015-03-31

Project acronymBRAINBALANCE

ProjectRebalancing the brain:
Guiding brain recovery after stroke

Researcher (PI)Alexander Thomas Sack

Host Institution (HI)UNIVERSITEIT MAASTRICHT

Call DetailsStarting Grant (StG), SH4, ERC-2010-StG_20091209

SummaryDamage to parietal cortex after stroke causes patients to become unaware of large parts of their surroundings and body parts. This so-called spatial neglect is hypothesised to be brought about by a stroke-induced imbalance between the left and right hemisphere. Some patients experience a partial recovery of lost abilities, but the factors that drive this rebalancing are unknown. The research proposed here will overcome this bottleneck in our understanding of the brain recovery phenomenon, and develop therapeutic approaches that for the first time will control, steer and speed up brain rebalancing after stroke. To that goal, we introduce a revolutionary approach in which TMS, fMRI, and EEG are applied simultaneously in healthy human volunteers to artificially unbalance the brain, and then study and control processes of rebalancing. Because we are one of the few groups worldwide that has accomplished this methodology, and that has the expertise to fully analyse the data it will yield, we are in a unique position to deliver both fundamental insights into brain plasticity, and derived new therapies. In brief, we will use TMS to (i) mimic spatial neglect in healthy volunteers while simultaneously monitoring the underlying neural network effects using fMRI/EEG, and to (ii) determine which exact brain reorganisation leads to an optimal behavioral recovery after injury. Importantly, we will use cutting-edge fMRI pattern recognition and machine learning algorithms to predict which concrete TMS treatment will specifically support this optimal functional reorganisation in the unbalanced brain. Finally, we will directly translate these fundamental findings into clinical practise and apply novel TMS protocols to rebalance the brain in patients suffering from parietal stroke.

Damage to parietal cortex after stroke causes patients to become unaware of large parts of their surroundings and body parts. This so-called spatial neglect is hypothesised to be brought about by a stroke-induced imbalance between the left and right hemisphere. Some patients experience a partial recovery of lost abilities, but the factors that drive this rebalancing are unknown. The research proposed here will overcome this bottleneck in our understanding of the brain recovery phenomenon, and develop therapeutic approaches that for the first time will control, steer and speed up brain rebalancing after stroke. To that goal, we introduce a revolutionary approach in which TMS, fMRI, and EEG are applied simultaneously in healthy human volunteers to artificially unbalance the brain, and then study and control processes of rebalancing. Because we are one of the few groups worldwide that has accomplished this methodology, and that has the expertise to fully analyse the data it will yield, we are in a unique position to deliver both fundamental insights into brain plasticity, and derived new therapies. In brief, we will use TMS to (i) mimic spatial neglect in healthy volunteers while simultaneously monitoring the underlying neural network effects using fMRI/EEG, and to (ii) determine which exact brain reorganisation leads to an optimal behavioral recovery after injury. Importantly, we will use cutting-edge fMRI pattern recognition and machine learning algorithms to predict which concrete TMS treatment will specifically support this optimal functional reorganisation in the unbalanced brain. Finally, we will directly translate these fundamental findings into clinical practise and apply novel TMS protocols to rebalance the brain in patients suffering from parietal stroke.

Max ERC Funding

1 344 853 €

Duration

Start date: 2011-04-01, End date: 2016-03-31

Project acronymBRAINBELIEFS

ProjectProving or improving yourself: longitudinal effects of ability beliefs on neural feedback processing and school outcomes

Researcher (PI)Nienke VAN ATTEVELDT

Host Institution (HI)STICHTING VU

Call DetailsStarting Grant (StG), SH4, ERC-2016-STG

SummaryTo successfully complete secondary education, persistent learning behavior is essential. Why are some adolescents more resilient to setbacks at school than others? In addition to actual ability, students’ implicit beliefs about the nature of their abilities have major impact on their motivation and achievements. Ability beliefs range from viewing abilities as “entities” that cannot be improved much by effort (entity beliefs), to believing that they are incremental with effort and time (incremental beliefs). Importantly, ability beliefs shape which goals a student pursues at school; proving themselves (performance goals) or improving themselves (learning goals). The central aims of the proposal are to unravel 1) the underlying processing mechanisms of how beliefs and goals shape resilience to setbacks at school and 2) how to influence these mechanisms to stimulate persistent learning behavior.
Functional brain research, including my own, has revealed the profound top-down influence of goals on selective information processing. Goals may thus determine which learning-related information is attended. Project 1 jointly investigates the essential psychological and neurobiological processes to unravel the longitudinal effects of beliefs and goals on how the brain prioritizes information during learning, and how this relates to school outcomes. Project 2 reveals how to influence this interplay with the aim to long-lastingly stimulate persistent learning behavior. I will move beyond existing approaches by introducing a novel intervention in which students experience their own learning-related brain activity and its malleability.
The results will demonstrate how ability beliefs and goals shape functional brain development and school outcomes during adolescence, and how we can optimally stimulate this interplay. The research has high scientific impact as it bridges multiple disciplines and thereby provides a strong impulse to the emerging field of educational neuroscience.

To successfully complete secondary education, persistent learning behavior is essential. Why are some adolescents more resilient to setbacks at school than others? In addition to actual ability, students’ implicit beliefs about the nature of their abilities have major impact on their motivation and achievements. Ability beliefs range from viewing abilities as “entities” that cannot be improved much by effort (entity beliefs), to believing that they are incremental with effort and time (incremental beliefs). Importantly, ability beliefs shape which goals a student pursues at school; proving themselves (performance goals) or improving themselves (learning goals). The central aims of the proposal are to unravel 1) the underlying processing mechanisms of how beliefs and goals shape resilience to setbacks at school and 2) how to influence these mechanisms to stimulate persistent learning behavior.
Functional brain research, including my own, has revealed the profound top-down influence of goals on selective information processing. Goals may thus determine which learning-related information is attended. Project 1 jointly investigates the essential psychological and neurobiological processes to unravel the longitudinal effects of beliefs and goals on how the brain prioritizes information during learning, and how this relates to school outcomes. Project 2 reveals how to influence this interplay with the aim to long-lastingly stimulate persistent learning behavior. I will move beyond existing approaches by introducing a novel intervention in which students experience their own learning-related brain activity and its malleability.
The results will demonstrate how ability beliefs and goals shape functional brain development and school outcomes during adolescence, and how we can optimally stimulate this interplay. The research has high scientific impact as it bridges multiple disciplines and thereby provides a strong impulse to the emerging field of educational neuroscience.

Max ERC Funding

1 597 291 €

Duration

Start date: 2017-03-01, End date: 2022-02-28

Project acronymBRAINDEVELOPMENT

ProjectHow brain development underlies advances in cognition and emotion in childhood and adolescence

Researcher (PI)Eveline Adriana Maria Crone

Host Institution (HI)UNIVERSITEIT LEIDEN

Call DetailsStarting Grant (StG), SH4, ERC-2010-StG_20091209

SummaryThanks to the recent advances in mapping brain activation during task performance using functional Magnetic Resonance Imaging (i.e., studying the brain in action), it is now possible to study one of the oldest questions in psychology: how the development of neural circuitry underlies the development of cognition and emotion. The ‘Storm and Stress’ of adolescence, a period during which adolescents develop cognitively with great speed but are also risk-takers and sensitive to opinions of their peer group, has puzzled scientists for centuries. New technologies of brain mapping have the potential to shed new light on the mystery of adolescence. The approach proposed here concerns the investigation of brain regions which underlie developmental changes in cognitive, emotional and social-emotional functions over the course of child and adolescent development.
For this purpose I will measure functional brain development longitudinally across the age range 8-20 years by using a combined cross-sectional longitudinal design including 240 participants. Participants will take part in two testing sessions over a four-year-period in order to track the within-subject time courses of functional brain development for cognitive, emotional and social-emotional functions and to understand how these functions develop relative to each other in the same individuals, using multilevel models for change. The cross-sectional longitudinal assessment of cognitive, emotional and social-emotional functional brain development in relation to brain structure and hormone levels is unique in the international field and has the potential to provide new explanations for old questions. The application of brain mapping combined with multilevel models for change is original, and allows for the examination of developmental trajectories rather than age comparisons. An integrative mapping (i.e., combined with task performance and with biological markers) of functional brain development is important not only for theory development, but also for understanding how children learn new tasks and participate in a complex social world, and eventually to tailor educational programs to the needs of children.

Thanks to the recent advances in mapping brain activation during task performance using functional Magnetic Resonance Imaging (i.e., studying the brain in action), it is now possible to study one of the oldest questions in psychology: how the development of neural circuitry underlies the development of cognition and emotion. The ‘Storm and Stress’ of adolescence, a period during which adolescents develop cognitively with great speed but are also risk-takers and sensitive to opinions of their peer group, has puzzled scientists for centuries. New technologies of brain mapping have the potential to shed new light on the mystery of adolescence. The approach proposed here concerns the investigation of brain regions which underlie developmental changes in cognitive, emotional and social-emotional functions over the course of child and adolescent development.
For this purpose I will measure functional brain development longitudinally across the age range 8-20 years by using a combined cross-sectional longitudinal design including 240 participants. Participants will take part in two testing sessions over a four-year-period in order to track the within-subject time courses of functional brain development for cognitive, emotional and social-emotional functions and to understand how these functions develop relative to each other in the same individuals, using multilevel models for change. The cross-sectional longitudinal assessment of cognitive, emotional and social-emotional functional brain development in relation to brain structure and hormone levels is unique in the international field and has the potential to provide new explanations for old questions. The application of brain mapping combined with multilevel models for change is original, and allows for the examination of developmental trajectories rather than age comparisons. An integrative mapping (i.e., combined with task performance and with biological markers) of functional brain development is important not only for theory development, but also for understanding how children learn new tasks and participate in a complex social world, and eventually to tailor educational programs to the needs of children.

SummaryOur ability to think, to memorize and focus our thoughts depends on acetylcholine signaling in the brain. The loss of cholinergic signalling in for instance Alzheimer’s disease strongly compromises these cognitive abilities. The traditional view on the role of cholinergic input to the neocortex is that slowly changing levels of extracellular acetylcholine (ACh) mediate different arousal states. This view has been challenged by recent studies demonstrating that rapid phasic changes in ACh levels at the scale of seconds are correlated with focus of attention, suggesting that these signals may mediate defined cognitive operations. Despite a wealth of anatomical data on the organization of the cholinergic system, very little understanding exists on its functional organization. How the relatively sparse input of cholinergic transmission in the prefrontal cortex elicits such a profound and specific control over attention is unknown. The main objective of this proposal is to develop a causal understanding of how cellular mechanisms of fast acetylcholine signalling are orchestrated during cognitive behaviour.
In a series of studies, I have identified several synaptic and cellular mechanisms by which the cholinergic system can alter neuronal circuitry function, both in cortical and subcortical areas. I have used a combination of behavioral, physiological and genetic methods in which I manipulated cholinergic receptor functionality in prefrontal cortex in a subunit specific manner and found that ACh receptors in the prefrontal cortex control attention performance. Recent advances in optogenetic and electrochemical methods now allow to rapidly manipulate and measure acetylcholine levels in freely moving, behaving animals. Using these techniques, I aim to uncover which cholinergic neurons are involved in fast cholinergic signaling during cognition and uncover the underlying neuronal mechanisms that alter prefrontal cortical network function.

Our ability to think, to memorize and focus our thoughts depends on acetylcholine signaling in the brain. The loss of cholinergic signalling in for instance Alzheimer’s disease strongly compromises these cognitive abilities. The traditional view on the role of cholinergic input to the neocortex is that slowly changing levels of extracellular acetylcholine (ACh) mediate different arousal states. This view has been challenged by recent studies demonstrating that rapid phasic changes in ACh levels at the scale of seconds are correlated with focus of attention, suggesting that these signals may mediate defined cognitive operations. Despite a wealth of anatomical data on the organization of the cholinergic system, very little understanding exists on its functional organization. How the relatively sparse input of cholinergic transmission in the prefrontal cortex elicits such a profound and specific control over attention is unknown. The main objective of this proposal is to develop a causal understanding of how cellular mechanisms of fast acetylcholine signalling are orchestrated during cognitive behaviour.
In a series of studies, I have identified several synaptic and cellular mechanisms by which the cholinergic system can alter neuronal circuitry function, both in cortical and subcortical areas. I have used a combination of behavioral, physiological and genetic methods in which I manipulated cholinergic receptor functionality in prefrontal cortex in a subunit specific manner and found that ACh receptors in the prefrontal cortex control attention performance. Recent advances in optogenetic and electrochemical methods now allow to rapidly manipulate and measure acetylcholine levels in freely moving, behaving animals. Using these techniques, I aim to uncover which cholinergic neurons are involved in fast cholinergic signaling during cognition and uncover the underlying neuronal mechanisms that alter prefrontal cortical network function.